Pediatric Respiratory Syncytial Virus Hospitalizations and Respiratory Support After the COVID-19 Pandemic

Key Points Question How did demographics and clinical outcomes of pediatric patients with respiratory syncytial virus (RSV) infection who required hospitalization and advanced respiratory support differ during the 2022 to 2023 post–COVID-19 pandemic season compared with prepandemic seasons? Findings In this cross-sectional study of 288 816 children 5 years or younger from 48 US pediatric hospitals, there was a surge in RSV infections during the 2022 to 2023 postpandemic season, with a 70% increase in children requiring advanced respiratory support. Children requiring respiratory support during the surge were older and had fewer comorbidities than in prepandemic seasons. Meaning These findings highlight postpandemic trends in advanced respiratory support use for pediatric RSV infections that can help inform guidelines as new RSV vaccines become more widely available.


Introduction
6][17] Pediatric RSV infections resurged in 2022 to 2023 after the removal of social distancing and masking, 18 resulting in a substantially increased number of hospitalizations and intensive care unit (ICU) admissions. 19,20[23] Palivizumab, a monoclonal antibody vaccine against RSV F protein, has been the only available licensed product for RSV prophylaxis, but it is limited to use in high-risk infants, is prohibitively expensive, [24][25][26] and reduces hospitalizations but not mortality. 27,28New opportunities for RSV prevention in infants and young children are now available for the first time in decades. 29In 2023, the US Food and Drug Administration approved an RSV vaccine for pregnant women 30 and a longacting RSV-neutralizing monoclonal antibody for children, both of which show promise for protecting young children against medically attended RSV lower respiratory tract infection. 31Historically, most RSV-infected children requiring hospitalization are previously healthy, 1,4,32 and children with medical comorbidities, including prematurity, heart disease, and chronic lung disease, have increased morbidity and mortality. 6,7,33Severe pediatric RSV infection is managed with advanced respiratory support modes, including high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), or invasive mechanical ventilation (IMV) and, less frequently, high-frequency ventilation (HFV), extracorporeal membrane oxygenation (ECMO), and inhaled nitric oxide (iNO). 4During the past decade, technological advances have facilitated increased use of HFNC and NIV for bronchiolitis, [34][35][36] with comparably stable IMV use. 37More data are needed to better understand the shifting landscape of pediatric RSV infection in the postpandemic era to identify populations that develop severe RSV infection and may benefit from newly available prophylactic strategies.This analysis compares the clinical outcomes of children with RSV 5 years or younger before, during, and after the COVID-19 pandemic.We hypothesized that the postpandemic 2022 to 2023 RSV season would identify an older, previously healthy population requiring hospitalization, intensive care, and advanced modes of respiratory support in altered numbers and proportions than prepandemic RSV seasons.

Patient Selection
The PHIS database was queried to identify patients 5 years or younger presenting to hospitals with RSV infection between July 1, 2017, and June 30, 2023.This patient population was selected to account for demographic shifts in age distribution observed clinically in the postpandemic season.
Hospitals were included if data were available for all study period quarters.Patients were identified by principal admission diagnoses using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes J20.5, J21.0, J12.1, and B97.4 for RSV infection.

Data Extraction
Demographic variables collected for each patient encounter during the study period included age (grouped as 0-12 months, 12-24 months, and Ն24 months), sex, race and ethnicity, and Child Opportunity Index 2.0 score.Clinical characteristics included level of service (emergency department [ED], inpatient, ICU, or neonatal ICU), hospital admission and discharge dates, and presence of complex chronic conditions as identified by the "complex chronic condition" flag in the PHIS database. 40Race and ethnicity data were included based on previous data highlighting the exacerbation of racial and ethnic disparities in health care access during and after the COVID-19 pandemic, and these data were obtained via the PHIS database. 41Outcomes assessed included hospital and ICU length of stay (LOS), use of respiratory support, cardiopulmonary resuscitation, ECMO, iNO, and in-hospital mortality.Mode of respiratory support was queried using the Clinical Transaction Classification codes (Truven Health Analytics) 42 for HFNC, NIV, IMV, and HFV.
Noninvasive ventilation included continuous positive airway pressure, bilevel positive airway pressure, noninvasive positive pressure ventilation, and intermittent positive pressure breathing.
Children's Hospital Association remapped PHIS HFNC codes in March 2023 and retroactively applied this coding to PHIS encounters from January 2016 onward, addressing previous limitations to including HFNC data. 43The HFNC data were available from 33 of the 48 study hospitals.The RSV seasons were defined from July 1 to June 30 to account for winter-predominant virus seasonality.
The prepandemic period was defined as 3 RSV seasons preceding the COVID-19 pandemic: 2017 to 2018, 2018 to 2019, and 2019 to 2020.The postpandemic RSV season was defined as 2022 to 2023.

Statistical Analysis
Data are reported as medians (IQRs) for continuous variables and numbers (percentages) for categorical variables.The Kruskal-Wallis test was used for continuous variables, and the Pearson χ 2 test or Cochran-Armitage χ 2 test for trend was used for categorical variables to assess statistical differences.Comparisons between the prepandemic and 2022 to 2023 postpandemic RSV seasons were performed using the Wilcoxon rank sum test.Totaled hospital-, ICU-, and respiratory supportdays (HFNC, NIV, IMV, and ECMO) were calculated using Clinical Transaction Classification codes.A 2-tailed P < .05 was considered statistically significant.All analyses were performed with Stata software, version 17.1 (StataCorp LLC).

Hospital Course
Although the total number of patients admitted to the hospital and ICU during the 2022 to 2023 postpandemic season was higher than in prepandemic seasons, a lower proportion of patients with RSV presenting for care required hospitalization (53.6% vs 68.3% before the pandemic; P < .001) (Figure 2A   patients with a 1-day LOS (26.1% vs 22.7%; P < .001)(Figure 2C) and fewer with a greater than 3-day LOS (34.1% vs 40.3%;P < .001)(Figure 2C).Similarly, ICU stays were shorter during the postpandemic season with fewer patients requiring ICU admission greater than 3 days (36.8% vs 42.2%; P < .001)(Figure 2D and Table ).Although the total number of deaths during hospitalization for RSV increased by 28.3% in the 2022 to 2023 postpandemic season compared with the prepandemic mean (68 vs 53; P = .007)(eFigure 1A and eTable 1 in Supplement 1), the mortality rate was lower in the total hospitalized population (0.13% vs 0.20%; P = .007)(eFigure 1A and eTable 1 in Supplement 1).Of note, the mortality rate among ICU patients was not different in the prepandemic and postpandemic RSV seasons (0.47% vs 0.53%) (eFigure 1A and eTable 1 in Supplement 1).
Cardiopulmonary resuscitation (CPR) is a rare event in the pediatric RSV population, and a lower proportion of ICU patients required CPR during the 2022 to 2023 postpandemic season (0.32% vs 0.67%; P < .001)(eFigure 1B in Supplement 1).

Figure 1 .
Figure 1.Hospital Presentations, Hospital-and Intensive Care Unit (ICU)-Days, and Patient Age by Respiratory Syncytial Virus (RSV) Season

Figure 2 .
Figure 2. Hospital and Intensive Care Unit (ICU) Admissions and Length of Stay by Respiratory Syncytial Virus (RSV) Season

Figure 3 .F
Figure 3. Respiratory Support Mode Use by Respiratory Syncytial Virus (RSV) Season

Table .
Patient Characteristics (continued) Kruskal-Wallis test was used for continuous variables and Pearson χ 2 test and Cochran-Armitage χ 2 test for trend for categorical variables.Comparisons between prepandemic and postpandemic seasons were performed using the Wilcoxon rank sum test.Includes patients denoted as "other" in the Pediatric Health Information System database and those who declined to provide race and ethnicity information.HFNC data were only available from 33 of the 48 study hospitals; therefore, the denominator is different from other respiratory support types.Proportions were calculated based on the percentage of inpatients admitted to those 33 hospitals.
a Prepandemic data are reported as means.Percentages are reported as the frequency among all patients unless otherwise indicated.b c d